P1350: THE EFFICACY OF UPFRONT HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANTATION IN DECREASING RELAPSE RATE IN IV STAGE AND HIGH-INTERMEDIATE/HIGH IPI RISK GROUPS DLBCL
Authors: A. Koviazin, L. Filatova, I. Zyuzgin, A. Artemyeva, M. Motalkina, Y. Chudinovskikh, S. Volchenkov, I. Poliatskin, E. Dobrovolskaya, S. Shalaev, I. Ishmatova, A. Zverkova, D. Burda, S. Elkhova, T. Semiglazova
Journal: HemaSphere (2022)

Background: Approximately 30% of patients(pts) with IPI≥2 diffuse large B-cell lymphoma(DLBCL) have relapsed after the frontline regimens. Upfront high-dose chemotherapy(HDCT) with autologous hematopoietic stem cell transplantation(auto-HSCT) can be an effective option to decrease the relapse rate and increase the response rate in these patients. Aims: To determine the significance of the upfront HDCT with auto-HSCT in decreasing relapse rate and increased response rate for IV stage DLBCL pts with unfavorable prognosis. Methods: Included 105 pts: DLBCL NOS, age 18-65, stage IV, IPI≥2, CR/PR after x6 CHOP/EPOCH+R from 2010 to 2019 at NMRC of Oncology named after N.N.Petrov of MoH of Russia were retrospectively analyzed. HSCT group (G1) includes pts with upfront HDCT followed by auto-HSCT (n=35). The control group (G2) includes pts with non-invasive follow-up after induction only (n=70). Groups had equal mean (53,4±21.2 mon in G1 vs 48,9±12.5 mon in G2, p=0.71) observation period and mean (48.0±11.7 yrs in G1 vs 48.9±12.5 yrs in G2, p=0.72) age. No difference was in sex (51% (18/35) men in G1 vs 45.7% (32/70) in G2, p = 0.67), IPI (71.4% (25/35) IPI≥3 pts in G1 vs 58.5% (41/70) IPI≥3 pts in G2, p=0.28) or extranodal (E) involvement (77.1% (27/35) pts with >1 E in G1 vs 71.4% (50/70) in G2, p=0.69). Extra with lung lesions (EL) was detected in 20% (7/35) pts in G1 vs 21,4% (15/70, p=0.86) in G2; with adrenal lesions (EA) in 20% (7/35) pts in G1 vs 6% (4/66, p=0.055) in G2. MYC and BCL-2 coexpression were analyzed in 100% (35/35) pts samples in G1 and in 74.2% (52/70) samples in G2 and were present in 37% (13/35) G1 pts and 31/52 G2 pts, p=0.0503. Between-group comparisons were conducted using a χ2, χ2 with Yates correction(Yates), Fisher’s exact test or McNemar criteria with Yates in paired samples for categorical variables and a two-sided independent t-test for continuous variables. A two-sided p-value of <0.05 significance level was considered to be statistically significant in all analyses. Results: Upfront HSCT significantly increased number of complete responses(CR) from 63% (22/35) after induction to 100% (35/35) after HSCT, p = 0.0009. Early relapse rate (RR) was significantly lower in G1 pts (2.8%(1/35) in HSCT vs 21.4%(15/70) in G2, p=0,027). Overall RR was borderline (8.5%(3/35) in G1 vs 27.1%(19/70) in G2, p=0,051). In combined group analysis, early RR was significanty lower in pts with double-expressor lymphomas (DEL) treated by upfront HSCT - 0%(0/13) in G1 vs 57.1%(12/21) in G2, p<0.001. Also, DEL was a worsening factor in overall RR(0% (0/13) in G1 vs 66.6%(14/21) in G2, p=0.013). Lung E significantly increased overall RR in control group (0%(0/7) in G1 vs 60%(9/15) in G2, p=0.021). In subgroup analysis no significant factors for overall and early RR were detected in HSCT group. In control group early RR was higher if pts had DEL (57.1%(12/21) DEL+ vs 16.1%(5/31) DEL-, p=0.003) or EA (75%(3/4) EA+ vs 24.2%(16/66) EA-, p=0.041). Overall RR was significantly increased in pts with DEL (66.6%(14/21) DEL+ vs 16.1%(5/31) DEL-, p<0,001) and with EL(60%(9/15) EL+ vs 18.1%(10/55) EL-, p=0.04). Summary/Conclusion: 1. Complete response rate significantly increased in 18-65 yrs, DLBCL NOS, IV stage, IPI≥2 pts treated by upfront HSCT. 2. Upfront HSCT significantly decreasing early RR and have tend to decrease overall RR in 18-65 yrs, DLBCL NOS, IV stage, IPI≥2 pts. 3. Double-expressor lymphoma increasing overall and early RR in 18-65 yrs, DLBCL NOS, IV stage, IPI≥2 pts. More than one site extranodal involvement with lung or adrenal lesions increasing overall and early RR correspondingly.